It has been known for some time that vitamin D and a number of hormones influence the intestinal transport mechanisms for calcium, but the precise nature of their interaction with this system is still unknown. It is hoped that through a study of the biochemical effects of vitamin D and hormones at the cellular level, as well as their mutual effects on calcium transport across biological membranes, the proposed research will provide further insight into the biochemical basis for certain of the known physiologic effects of the hormones as well as the vitamin. Information obtained in the course of these studies should also advance our understanding of the biophysical and biochemical properties of the intestinal absorptive process as well as those factors regulating transport across biologic membranes in general. The purpose of the present investigation is to evaluate the potential role of factors such as vitamin D, cyclic nucleotides and certain hormones in the regulation of intestinal calcium transport. In addition, attempts will be made to define the relative contributions of changes in the active (cellular) and diffusional (cellular and extracellular or shunt) pathways to the regulation of these processes. Finally, the role of the ileum as an excretory organ for calcium, iron, strontium and other trace metals will be assessed. The proposed studies will involve measurements of influx at the luminal surface and bidirectional transmural fluxes with the mucosa short-circuited and clamped at various transmural potential differences. In addition, an attempt will be made to define the calcium uptake and release processes in microvillus and basolateral membrane vesicles. Finally, we will try to identify membrane components related to vitamin D action, and evaluate the role of cyclic nucleotide-dependent protein kinases. With these techniques one should be able to define the nature of the factos regulating intestinal calcium movement, and the pathways through which calcium crosses the intestine. Finally, the importance of the ileum in the maintaining the balance of other polyvalent metals will be assessed by measuring their transmural fluxes under short-circuited conditions.